Project Summary During my PhD, I used skeletal myogenesis as my model to dissect signal transduction and gene regulation mechanisms. I have obtained technical literacy over a wide range of molecular biology and biochemical tools, accumulated critical experience on genetic mouse models, and developed critical and analytical thinking skills in experimental biology. I also came to appreciate the power of functional genomics, My so far 4.5-year's postdoc training focuses on interrogating molecular drivers in skin tumorigenesis fueled by stem cells, applying principles of functional genomics in mouse models, and validating findings in human clinic samples and xenografts. These training had expanded my research horizon, matured my experimental skills, and laid groundwork for me to ask important questions in human diseases. As I extend my training due to unexpected family difficulties, it would be essential for me to acquire additional scientific and academic skills that will enable me to gain full research autonomy and develop an innovative basic research program addressing fundamental questions in development and diseases. Over the past decades, we start to understand some of the molecular mechanisms involved in wound repair. We have also acquired substantial insights into oncogenic and tumor suppressive pathways in cancer. However, despite the long posited hypothesis that cancer is a wound that never heals, it is still unclear whether wounds and cancer functionally rely on the same stress components and if so, at which point they diverge. These are the primary focus of my current and future proposed research. I will establish and expand tools based on non- germline genetically engineered mosaic mouse models using in utero transduced CRISPR reagents. I will apply functional genomic approaches to prioritize and screen a focused list of stress relevant genes in driving wound repair and cancer. I will delineate molecular mechanisms that steer the long sought bifurcation point between the two stress conditions, and validate the physiological relevance of top my candidate stress genes in human samples. This knowledge will add to our understanding of the molecular mechanisms during cellular stress, and help to improve therapeutic treatments in skin wounds, hyperplasic diseases, and cancer. With the stimulating atmosphere provided by the Fuchs lab, the Rockefeller University, the Tri- Institution, and the broader NYC scientific community, I found myself positioned within an exceptional environment to pursue my ambition. If awarded, I will further obtain training in 1) technical skills ? sequencing, advanced microscopy, CRISPR technology; and 2) personal development ? writing, communication, mentoring, leadership, and management. My goal is, during the final years of K01, land in an independent tenure-track position with top-tier vibrating environment, especially those with an intensive emphasis on non-coding biology, where I will establish my own innovative, viable and sustainable research program in skin diseases and cancer.